The invention pertains to a device for the investigation of biological vessels, preferably of retinal vessels, in which at least one vessel section is present as an electronic image or as a series of electronic images, said image(s) being supplied from a photoelectric receiving device to an evaluation unit. The invention can be applied for functional diagnosis and analysis of all optically accessible blood vessels, or vessels that can be imaged by other means. Preferably it is used for the examination of vessel behavior of the large retinal vessels. However, it can also be used for the examination of vessels of the iris, the conjunctiva and also of vessels which are optically accessible with a microscope or endoscope or by other means. In particular, vessels which are exposed during an operation, can be monitored and examined by means of a surgical microscope. The application of the invention is possible both to human blood vessels and also for the examination of animals. The imaging of vessels can take place by means of optical imaging systems with optical-electronic image conversion, or by means of electronic image generating systems, e.g., scanning of photographic vessel images. Its application is not restricted solely to the examination of vessels in the microcirculation, but rather it can also be employed in a favorable manner for large images of vessel sections created by means of ultrasound and other imaging principles. In the state of the art for examination of vessels, dilatation measurements of vessels in the back of the eye are known. These methods are based on the use of optical, precision measurement techniques in an ophthalmoscopic image, the use of precision optical measurement techniques and densitometry of the photographic negative or are based on photoelectric measurement methods.
According to DE 3,839,272 an apparatus is known for measuring the background of the eye, which is suitable for clinical purposes and which allows a measurement of dilated vessels, whereby the objective acquisition of tiny, pulsating, auto-regulative or local-regulative changes in vessel dilation is possible. In this case one image field with vessels of the eye background is imaged on at least two CCD line segments, whereby means are provided to change the image position and optical properties of the image. The apparatus can be operated in continuous mode or in flash mode. Likewise, the Suzuki, Y. (Surv. Ophthalmol. 1995, May; 39 Suppl. 1: 57-65) measurement station works with a CCD line. The disadvantages of the mentioned designs consist in that only quasi-continuous measurements are possible with single CCD lines, and with somewhat improved reproducibility compared to the state of the art, but still only with large systematic errors between the seatings and over the course of examinations. Clinically relevant, meaningful information is only obtained as a group average. The complex behavior of the vessels, including also the disclosure of free, local regulative vessel responses and pulsatory changes, are not reliable in a particular case and usually are not even detectable.
Various devices or methods are described to acquire the pulse shape of the retina vessels through the use of pulse-synchronous TV images or photographic images. For studies of this type, through the additional acquisition of pulse signals, the image recordings or digitizing can be controlled synchronous with the pulse. In this regard a device and a method are described in U.S. Pat. No. 5,031,632 with which the pulse shape of only one site of a vessel can be determined on-line from a pulse-synchronous TV image sequence. However, the proposed solution has a fundamental, exceptionally large measurement uncertainty which will not allow a clinically relevant, individual acquisition of the pulse shape of retinal vessel diameter. The disclosed pulse shapes do not correspond to the actual pulse shapes, as are measurable based on the diameter of the retina vessel.
A similar method is described by Dumskyi et al. (1996 Curr Eye Res. 1996 June; 15(6); 652-632). These methods do not have on-line capability, are very time-consuming and too inaccurate and likewise are of value only for statements about a group average.
Another photoelectric method was presented by Delori (Applied Optics Vol. 27, No 6,1988, 1113-1125), in which the vessel diameter is also determined. The measurement principle differs fundamentally from the proposed solution to be described below. A small, gap-like measuring surface scans under different color, extremely narrow-band illumination at one site of the vessel perpendicular to the vessel run across the vessel diameter and the resultant brightness profiles are location-corrected and combined into a summary profile, from which then the vessel diameter is calculated from the very error-laden half-value width of the edges. Large systematic error sources, in particular due to movements of the eyexe2x80x94which cannot be corrected entirely with the stated principlexe2x80x94in particular eye motions during the scan processxe2x80x94which cannot be corrected at allxe2x80x94affect the measured result. In principle, the measuring system can provide only quasi-continuous measured values with measurement times of about 1.6 to 3 s.
Sometimes tests are described in the literature for use of standard methods of image processing or complicated mathematic algorithms for acquiring the diameter of the retinal vessels. For example, Schack et al. (Mustererkennung 1994, Springer-Pub., 475-481) describe special adaptive methods, but they do not allow the required accuracy nor do they have on-line capability, even though the mathematic principles are initially much more promising than the known and unsuitable standard method of image processing for edge recognition.
With previously known methods and devices, the reproducibility between the sittings has a very low accuracy. This reproducibility is not suitable for the significant detection of regulatory parameters and pathological and therapeutic changes of an individual vessel of a patient. Regulatory changes and also physiological rhythms of stochastic changes of vessel diameter exhibit differences of less than 10%, sometimes only 1 to 2%, and are not individually and significantly detectable with the known methods. The previous methods usually do not have on-line capability and/or do not have sufficient time resolution and/or are not practical for clinical use. The invention is based on the problem of defining a method and a corresponding device for the examination of vessels with which the complex vessel behavior can be determined.
According to this invention, the problem is solved by a device and by a method having the properties stated in the patent claims.
The invention is characterized by a number of advantages.
The invention creates the technical prerequisites for the continuous measurement of the vessel diameter in association with the quasi-simultaneous or precisely simultaneous acquisition of the temporal and local dependencies and their changes. Thus the biological variability formerly interpreted as a source of error, e.g., vasomotion, blood pressure waves and local changes in lumen, are determinable and clinically evaluable. Now surprisingly, physiological effects such as the Bayliss effect, Meyer waves, vasomotions, vessel changes related to location, po2- and pco2-changes can now be detected individually for single vessel sections and persons, but also in addition their temporal and local profile can be recorded along a vessel. Accordingly, we obtain an entirely new quality of examination of vessels in the microcirculation.
The invention makes possible not only the simultaneous, on-line acquisition of location-dependent and time-dependent variables, but also the simultaneous, on-line acquisition of several vessels.
The invention reduces the systematic error in measurements considerably, tangibly improves the reproducibility and makes possible the highly significant detection of pathologic, therapeutic or provoked changes in single sections of a vessel, individually for specific persons and thus for the first time creates the prerequisites for optimized, individual therapy from the viewpoint of vessel behavior.
The invention makes use of the potential for data acquisition and effective evaluation of a number of beneficial and new diagnostic methods for the evaluation of vessel behavior and is not restricted to the retina vessels.
Furthermore, the application of the invention makes it possible to form powerful parameters for formerly non-measurable retina vessels which can be displayed in a graphically concise manner and now allows for the first time, an evaluation of a number of measured values.
The special types of presentation are tailored to the specific bits of information, in particular the subsequent allocation of measured data obtained from the image, back into the correct image.
In addition, the invention makes it possible to obtain parameters from a spectral analysis of the vessel diameter.
Furthermore, it is helpful that the method has on-line capability using low-cost PC equipment due to the invented configuration.
An additional, important advantage consists in that the device according to this invention consists of various, special apparatus which can also be employed individually. Some of the most important ones are:
A fixation device according to the invention, with consistent fixation coordinates relative to the object space in the background of the eye, so that comparable measured results will be assured,
The placement of one or more help windows to reduce the influence of motions of the eye, and
the use of a measurement field so that the light stress on the eye is reduced.
The invented method and the invented apparatus allow a number of different implementations with different clinical findings to problem constellations which are of equal clinical relevance. As photoelectric receiver units, we can use both digital or analog recording systems for image sequences, and also imaging systems, such as laser scanner systems and conventional, optical imaging systems with optical-electronic imaging or any other systems that can supply an electronic image of a vessel section, so that the number of possible designs of the invention will be expanded even more.
The invention will be explained in greater detail below based on one design example. In this regard we will explain a measuring station for on-line examining of near-papilla retinal branch vessel sections. The clinical background is the question of the degree of local regulation and a search for the causes of limited local regulation pertaining to vasomotion or contractility function and vessel wall stiffness along the vessel sections. These clinical questions cannot be examined by any of the known methods.